Goldwater, along with incumbent Vice President Richard Nixon, were renominated by their party with little difficulty. Lyndon Johnson was initially the frontrunner for the Democratic Party's nomination, but Kennedy won nearly all of the primaries and caucuses, mostly due to the affluence of his family. Kennedy chose another party liberal, Senator Hubert Humphrey of Minnesota, to be his running mate.

Foreign Policy was the dominant theme throughout the election campaign, particularly Goldwater's conduct of the Cold War, the 1963 invasion of Cuba, and the escalation of hostilities in southeast Asia. Goldwater rallied public support for hawkish American policies, and simultaneously promised to work towards peace. Kennedy's positions were vauge and labelled by Goldwater as both extreme and flakey, even though Kennedy was likely more moderate than Goldwater. Both candidates were center-right and voiced opposition to civil rights for African-Americans and demanded social reforms.